CART neurons in the lateral hypothalamus communicate with the nucleus accumbens shell via glutamatergic neurons in paraventricular thalamic nucleus to modulate reward behavior

Background: Identifying neural substrates that are differentially affected by drugs of abuse and natural rewards is key to finding a target for an efficacious treatment for substance abuse. Melanin-concentrating hormone is a polypeptide with an inhibitory effect on the mesolimbic dopamine system. Here we test the hypothesis that melanin-concentrating hormone in the lateral hypothalamus and nucleus accumbens shell is differentially involved in the regulation of morphine and food-rewarded behaviors. Methods: Male Sprague–Dawley rats were trained with morphine (5.0 mg/kg, subcutaneously) or food pellets (standard chow, 10–14 g) to induce a conditioned place preference, immediately followed by extinction training. Melanin-concentrating hormone (1.0 µg/side) or saline was infused into the nucleus accumbens shell or lateral hypothalamus before the reinstatement primed by morphine or food, and locomotor activity was simultaneously monitored. As the comparison, melanin-concentrating hormone was also microinjected into the nucleus accumbens shell or lateral hypothalamus before the expression of food or morphine-induced conditioned place preference. Results: Microinfusion of melanin-concentrating hormone into the nucleus accumbens shell (but not into the lateral hypothalamus) prevented the reinstatement of morphine conditioned place preference but had no effect on the reinstatement of food conditioned place preference. In contrast, microinfusion of melanin-concentrating hormone into the lateral hypothalamus (but not in the nucleus accumbens shell) inhibited the reinstatement of food conditioned place preference but had no effect on the reinstatement of morphine conditioned place preference. Conclusions: These results suggest a clear double dissociation of melanin-concentrating hormone in morphine/food rewarding behaviors and melanin-concentrating hormone in the nucleus accumbens shell. Melanin-concentrating hormone could be a potential target for therapeutic intervention for morphine abuse without affecting natural rewards.

Download Full-text

Orexin signaling in rostral lateral hypothalamus and nucleus accumbens shell in the control of spontaneous physical activity in high- and low-activity rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00339.2016 ◽

2017 ◽

Vol 312 (3) ◽

pp. R338-R346 ◽

Cited By ~ 13

Author(s):

Claudio Perez-Leighton ◽

Morgan R. Little ◽

Martha Grace ◽

Charles Billington ◽

Catherine M. Kotz

Keyword(s):

Physical Activity ◽

Nucleus Accumbens ◽

Lateral Hypothalamus ◽

Receptor Expression ◽

Nucleus Accumbens Shell ◽

Orexin A ◽

Orexin Neuron ◽

Spontaneous Physical Activity ◽

Low Activity ◽

Higher Sensitivity

Spontaneous physical activity (SPA) describes activity outside of formal exercise and shows large interindividual variability. The hypothalamic orexin/hypocretin peptides are key regulators of SPA. Orexins drive SPA within multiple brain sites, including rostral lateral hypothalamus (LH) and nucleus accumbens shell (NAcSh). Rats with high basal SPA (high activity, HA) show higher orexin mRNA expression and SPA after injection of orexin-A in rostral LH compared with low-activity (LA) rats. Here, we explored the contribution of orexin signaling in rostral LH and NAcSh to the HA/LA phenotype. We found that HA rats have higher sensitivity to SPA after injection of orexin-A in rostral LH, but not in NAcSh. HA and LA rats showed similar levels of orexin receptor expression in rostral LH, and activation of orexin-producing neurons after orexin-A injection in rostral LH. Also, in HA and LA rats, the coinjection of orexin-A in rostral LH and NAcSh failed to further increase SPA beyond the effects of orexin-A in rostral LH. Pretreatment with muscimol, a GABAA receptor agonist, in NAcSh potentiated SPA produced by orexin-A injection in rostral LH in HA but not in LA rats. Our results suggest that a feedback loop from orexin-responsive neurons in rostral LH to orexin neurons and a the NAcSh–orexin neuron–rostral LH circuit regulate SPA. Overall, our data suggest that differences in orexin sensitivity in rostral LH and its modulation by GABA afferents from NAcSh contribute to individual SPA differences.

Download Full-text

Ipsilateral feeding-specific circuits between the nucleus accumbens shell and the lateral hypothalamus: Regulation by glutamate and GABA receptor subtypes

Neuropharmacology ◽

10.1016/j.neuropharm.2012.10.027 ◽

2013 ◽

Vol 67 ◽

pp. 176-182 ◽

Cited By ~ 17

Author(s):

Kevin R. Urstadt ◽

Peter Kally ◽

Sana F. Zaidi ◽

B. Glenn Stanley

Keyword(s):

Nucleus Accumbens ◽

Lateral Hypothalamus ◽

Gaba Receptor ◽

Receptor Subtypes ◽

Nucleus Accumbens Shell

Download Full-text

MC4-R signaling within the nucleus accumbens shell, but not the lateral hypothalamus, modulates ethanol palatability in rats

Behavioural Brain Research ◽

10.1016/j.bbr.2012.10.055 ◽

2013 ◽

Vol 239 ◽

pp. 51-54 ◽

Cited By ~ 8

Author(s):

Jose M. Lerma-Cabrera ◽

Francisca Carvajal ◽

Gabriela Chotro ◽

Mirari Gaztañaga ◽

Montserrat Navarro ◽

...

Keyword(s):

Nucleus Accumbens ◽

Lateral Hypothalamus ◽

Nucleus Accumbens Shell

Download Full-text

The Paraventricular Thalamus as a Critical Node of Motivated Behavior via the Hypothalamic-Thalamic-Striatal Circuit

Frontiers in Integrative Neuroscience ◽

10.3389/fnint.2021.706713 ◽

2021 ◽

Vol 15 ◽

Author(s):

Amanda G. Iglesias ◽

Shelly B. Flagel

Keyword(s):

Nucleus Accumbens ◽

Lateral Hypothalamus ◽

External Environment ◽

Glutamatergic Neurons ◽

Efferent Connections ◽

Motivated Behavior ◽

Internal States ◽

Paraventricular Thalamus ◽

Motivated Behaviors ◽

Anterior Posterior

In this review, we highlight evidence that supports a role for the paraventricular nucleus of the thalamus (PVT) in motivated behavior. We include a neuroanatomical and neurochemical overview, outlining what is known of the cellular makeup of the region and its most prominent afferent and efferent connections. We discuss how these connections and distinctions across the anterior-posterior axis correspond to the perceived function of the PVT. We then focus on the hypothalamic-thalamic-striatal circuit and the neuroanatomical and functional placement of the PVT within this circuit. In this regard, the PVT is ideally positioned to integrate information regarding internal states and the external environment and translate it into motivated actions. Based on data that has emerged in recent years, including that from our laboratory, we posit that orexinergic (OX) innervation from the lateral hypothalamus (LH) to the PVT encodes the incentive motivational value of reward cues and thereby alters the signaling of the glutamatergic neurons projecting from the PVT to the shell of the nucleus accumbens (NAcSh). The PVT-NAcSh pathway then modulates dopamine activity and resultant cue-motivated behaviors. As we and others apply novel tools and approaches to studying the PVT we will continue to refine the anatomical, cellular, and functional definitions currently ascribed to this nucleus and further elucidate its role in motivated behaviors.

Download Full-text